Dai Kesheng, Wang Yuedan, Yan Rong, Shi Quanwei, Wang Zhicheng, Yuan Yanhong, Cheng Hong, Li Suping, Fan Yubo, Zhuang Fengyuan
Department of Biological Science and Technology, Beijing University of Aeronautics and Astronautics, 37 Xueyuan Road, Haidian district, Beijing 100083, China.
Thromb Haemost. 2009 May;101(5):902-10.
Many serious thrombotic and haemorrhagic diseases or fatalities have been documented in human being exposed to microgravity or hypergravity environments, such as crewmen in space, roller coaster riders, and aircrew subjected to high-G training. Some possible related organs have been examined to explore the mechanisms underlying these gravity change-related diseases. However, the role of platelets which are the primary players in both thrombosis and haemostasis is unknown. Here we show that platelet aggregation induced by ristocetin or collagen and platelet adhesion to von Willebrand factor (VWF) were significantly decreased after platelets were exposed to simulated microgravity. Conversely, these platelet functions were increased after platelets were exposed to hypergravity. The tail bleeding time in vivo was significantly shortened in mice exposed to high-G force, whereas, was prolonged in hindlimb unloaded mice. Furthermore, three of 23 mice died after 15 minutes of -8 Gx stress. Platelet thrombi disseminated in the heart ventricle and blood vessels in the brain, lung, and heart from the dead mice. Finally, glycoprotein (GP) Ibalpha surface expression and its association with the cytoskeleton were significantly decreased in platelets exposed to simulated microgravity, and obviously increased in hypergravity-exposed platelets. These data indicate that the platelet functions are inhibited in microgravity environments, and activated under high-G conditions, suggesting a novel mechanism for gravity change-related haemorrhagic and thrombotic diseases. This mechanism has important implications for preventing and treating gravity change-related diseases, and also suggests that special attentions should be paid to human actions under different gravity conditions.
在暴露于微重力或超重力环境的人类中，已记录到许多严重的血栓形成和出血性疾病或死亡事件，例如太空船员、过山车乘客以及接受高重力训练的空勤人员。已经对一些可能相关的器官进行了检查，以探索这些与重力变化相关疾病的潜在机制。然而，作为血栓形成和止血主要参与者的血小板的作用尚不清楚。在此我们表明，在血小板暴露于模拟微重力后，瑞斯托菌素或胶原蛋白诱导的血小板聚集以及血小板与血管性血友病因子（VWF）的粘附显著降低。相反，在血小板暴露于超重力后，这些血小板功能增强。暴露于高重力的小鼠体内尾部出血时间显著缩短，而在后肢卸载的小鼠中则延长。此外，23只小鼠中有3只在 -8 Gx 应激15分钟后死亡。死亡小鼠的心脏心室以及脑、肺和心脏的血管中出现了血小板血栓。最后，暴露于模拟微重力的血小板中糖蛋白（GP）Ibalpha 的表面表达及其与细胞骨架的结合显著降低，而在暴露于超重力的血小板中则明显增加。这些数据表明，血小板功能在微重力环境中受到抑制，而在高重力条件下被激活，提示了一种与重力变化相关的出血性和血栓性疾病的新机制。这一机制对于预防和治疗与重力变化相关的疾病具有重要意义，也表明在不同重力条件下应特别关注人类行为。
